Studies refine amyloid imaging role in dementia
medwireNews: Two meta-analyses published in JAMA help to define the role of amyloid imaging in dementia.
The studies support the contention that amyloid deposition in cognitively normal people is a sign of impending Alzheimer’s disease (AD), and demonstrate the importance of amyloid imaging in supporting diagnosis in patients with early-onset dementia.
In an accompanying editorial, Roger Rosenberg (University of Texas Southwestern Medical Center at Dallas, USA) describes the studies as “succinct meta-analyses of considerable clinical value.”
“Together, these data show the immense potential clinical use of amyloid imaging to make the correct diagnosis in early-onset dementia”, he writes.
Both studies obtained individual patient data; the first included 2914 people with normal cognition, 697 with subject cognitive impairment and 3972 with mild cognitive impairment, aged between 18 and 100 years.
In the first study, researcher Willemijn Jansen (Maastricht University, the Netherlands) and team found that the presence of amyloid on positron emission tomography (PET) or in cerebrospinal fluid increased in line with risk factors for AD dementia – with age, APOE status and cognitive impairment. This supports the theory that the presence of amyloid in nondemented people indicates early AD, they say.
For example, amyloid positivity among people with normal cognition rose from 10.4% at age 50 years to 43.8% at age 90 years. At age 50 years, the prevalence of amyloid pathology was 5.7% in cognitively normal people without the APOE ε4 allele, but 14.9% in those who carried it, and these rates rose to 18.7% and 40.0%, respectively, among those with mild cognitive impairment.
Comparing their data with reported amyloid pathology in AD dementia, the researchers estimate that amyloid positivity precedes AD dementia diagnosis by 20 to 30 years. However, in line with the cognitive reserve hypothesis, participants with above-median levels of education had higher rates of amyloid pathology than less-educated participants, suggesting that education allows the brain to maintain function despite the presence of amyloid pathology.
The second study, by Rik Ossenkoppele (VU University Medical Center Amsterdam, the Netherlands) and co-authors, included 1359 AD patients, diagnosed clinically, and 538 patients with non-AD dementia, specifically, frontotemporal dementia, vascular dementia, dementia with Lewy bodies and corticobasal syndrome.
They found that amyloid pathology prevalence declined with age in AD patients, from 93% at age 50 years to 84% at age 80 years. By contrast, amyloid positivity at age 50 years was low in most other dementias, and in 1849 cognitively normal controls, but it rose with increasing age. As expected, amyloid positivity was more common in APOE ε4 carriers than noncarriers.
“This study underscores that clinical diagnosis, age, and APOE status are crucial factors when ordering and interpreting clinical amyloid PET scans”, write the researchers. Imaging may help to distinguish between AD and other dementias in their early stages, especially to rule-in AD, but should be interpreted with caution in older patients, they explain.
However, the age-related decline in amyloid positivity in AD patients was most marked in those not carrying the APOE ε4 allele, suggesting that amyloid imaging could also be useful to support clinical diagnosis in older AD patients without the risk allele.
Moreover, their findings from an independent sample of 1369 patients with AD-confirmed autopsy showed high agreement between imaging and autopsy, suggesting that imaging can be used as a rule-out for AD at any age.
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